Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Methylation arrays (MethylationEPIC) of cord and peripheral whole blood from children born to mothers with obesity or gestational diabetes, with longitudinal follow-up during their first year of life

ABSTRACT: Epidemiological studies have associated maternal metabolic conditions such as obesity and gestational diabetes with poor health outcomes in the offspring. Epigenetic mechanisms may help explain the intrauterine influence that mothers have on their offspring during pregnancy. Here, using Illumina's MethylationEPIC array technology, we have longitudinally profiled the blood methylomes of children born to mothers with obesity and obesity with gestational diabetes, and healthy controls, during the first year of life (measurements at 0, cord blood; 6 and 12 months, peripheral blood).

ORGANISM(S): Homo sapiens

SUBMITTER: Mario Fraga F.

PROVIDER: E-MTAB-12728 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The prevalence of metabolic syndrome comprising obesity, type 2 diabetes mellitus and cardiovascular disease has been on the rise world-wide in recent years. As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. Methods We have assessed primary umbilical cord derived cells such as human vascular endothelial cells (HUVECs) and Wharton’s jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and healthy mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, as well as the ability to support blood vessel growth. We conducted gene expression microarray studies with subsequent pathway analysis and candidate gene validation. Results We observed striking differences between the two groups such as lower metabolic rates and impairment of tube formation in cells with GDM background. HUVECs from subjects with maternal GDM have lower expression of the anti-apoptotic protein BCL-Xl suggesting compromised angiogenic capabilities. Comparative gene expression analysis revealed blood vessel formation as a major pathway enriched in the GDM derived HUVECs with the surface marker CD44 as a significant gene under-expressed in the GDM group. Functional validation of CD44 revealed that it regulates tube formation in HUVECs thereby providing new insights into a novel pathway imprinted in primary umbilical cord derived cells from GDM offspring. Conclusions/interpretation Our data demonstrate that primary cells isolated from the umbilical cord of offspring born to GDM mothers maintain metabolic and molecular imprints of maternal hyperglycemia, which occurred during prenatal development reflecting an enhanced risk for cardiovascular disease later in life.

Dataset Information

Methylation arrays (MethylationEPIC) of cord and peripheral whole blood from children born to mothers with obesity or gestational diabetes, with longitudinal follow-up during their first year of life

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